Mendelian 1:1 segregation ratio has been accepted in many theories in population genetics. The long-term goal of this project is to show that "non-Mendelian ratio" is in fact the general rule. Specific aim of this project is to re-establish a formal genetic basis of the elements of Segregation Distorter (SD) system in Drosophila melanogaster. The SD system has been known as one of the best examples of non-Mendelian segregation (meiotic drive). Studies on this model system will provide us with a good basis to approach the long-term goal described above. Several models have been proposed to explain the process of segregation distortion, but not all of the observations thus far made can be satisfactorily explained by those models. There is one common prediction among all the proposed models, i.e., in an Sd heterozygous Rsp (insensitive)/Rsp (sensitive) male, the chromosome carrying the Rsp (sensitive) allele is distorted, but the chromosome with the Rsp (insensitive) is not. However, this prediction was completely re-versed in some of my recent observations. I tentatively termed this phenomenon as negative segregation distortion and it appears to question the most basic concept of sensitivity and insensitivity of the Rsp alleles. Besides four basic elements of the SD system so far characterized, there must be several more in this system which play key- roles to determine the direction of segregation distortion (at least one in the second and at least one in the X chromosomes). Including these new elements, I plan to reestablish the formal genetic basis of segregation distortion once and for all. To do this, I will adopt the "inseminated female transfer" experimental scheme, instead of adopting the conventionally used mating scheme in which only a fraction of total progeny was sampled, such that the results will provide us with a better estimate of the "absolute values" but not of the "relative values". Results of these studies will require us to re-evaluate many of the population genetics predictions on human populations such as genetic damages due to exposure to irradiation and chemicals through generations.